Modulation of oxotremorine‐induced tremor by central β‐adrenoceptors

Hallberg, Heléne; Almgren, Olle

doi:10.1111/j.1748-1716.1987.tb08085.x

Cited by 12 publications

(2 citation statements)

References 19 publications

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“…In contrast to the specific effects of the (-)-enantiomer at β 2 -receptors, the local anaesthetic potency of both enantiomers was not different (Engelhardt, personal communications). Fourth, the anticonvulsant action of clenbuterol as well as the additive anticonvulsant effects in combination with phenobarbital were not influenced by the brainpermeable β 2 -receptor antagonist ICI 118.551 (O'Donnell 1997), tested at an adequately high dose (Hallberg and Almgren 1987;Murphy et al 1997). Fifth, repeated administration of clenbuterol (5 mg/kg s.c., twice daily for 14 days; comparable to literature data), which was demonstrated to decrease β (particularly β 2 )-receptor density (Finnegan et al 1987;Ordway et al 1987), showed no marked influence on the anticonvulsant effects of clenbuterol given alone or in combination with phenobarbital.…”

Section: Concentration-dependent Inhibition Of Peak I Namentioning

confidence: 97%

Anticonvulsant and sodium channel blocking activity of higher doses of clenbuterol

Fischer

Kittner

Regenthal

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

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Clenbuterol, a lipophilic beta2-adrenoceptor agonist, was investigated in various seizure models of experimental epilepsy. In the maximal electroshock seizure threshold test, clenbuterol (> or =4 mg/kg i.p.) increased the electroconvulsive threshold for tonic seizures in mice. In the traditional maximal electroshock seizure (MES) test in mice, ED50 values of 11 mg/kg i.p. or s.c. were determined. In both models, the beta2-receptor antagonist ICI 118.551 did not antagonize the anticonvulsant activity of clenbuterol. Combinations of clenbuterol with standard antiepileptics revealed additive anticonvulsant effects. Repeated administration of clenbuterol (5 mg/kg s.c., twice daily for 14 days) to mice did not significantly influence its anticonvulsant potency or the effectiveness of phenobarbital in the MES test. In various chemically-induced seizure tests with tonic convulsions, clenbuterol inhibited or tended to suppress the tonic phase. However, this drug was not effective in preventing clonic seizures in the pentylenetetrazol (85 mg/kg s.c.) seizure threshold test. In the rotarod ataxia test (mice), a minimal "neurotoxic" dose (TD50) of 41 mg/kg i.p. was determined. In unrestrained rats with chronically implanted electrodes in the dorsal hippocampus, clenbuterol (2 mg/kg and 4 mg/kg i.p.) significantly reduced the duration of electrically evoked hippocampal afterdischarges. In amygdala-kindled rats, clenbuterol (5 mg/kg and 10 mg/kg i.p.) reduced the seizure severity to stage 3. Additional studies indicated that clenbuterol (6 mg/kg i.p.) increased the heart rate and decreased the blood pressure, but this drug did not alter the plasma level of the two tested antiepileptics phenobarbital and carbamazepine. Furthermore, in whole-cell voltage-clamp experiments on cultured neonatal rat cardiomyocytes, clenbuterol (1-100 microM) depressed the fast sodium current in a concentration- and frequency-dependent manner. In conclusion, the anticonvulsant effects of higher doses of clenbuterol against generalized tonic-clonic and complex partial seizures seem to be related to the inhibition of voltage-dependent sodium channels and not to the modulation of beta-adrenoceptors.

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Section: Concentration-dependent Inhibition Of Peak I Namentioning

confidence: 97%

Anticonvulsant and sodium channel blocking activity of higher doses of clenbuterol

Fischer

Kittner

Regenthal

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

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“…By injecting into the CN substances which promote the hyperactivation of the cholinergic neurons and the formation of a GPEE, it is possible to induce an experimental form of the PS even without an insufficiency of DA and the DAergic apparatus. The phenomena of PS were reproduced by this method in animals of various species by the injection into the CN of oxytremorine, an agonist of the M-cholinoreceptors, and other cholinomimetics [18,21], as well as by the systemic administration of galantamine, a cholinesterase inhibitor [9].The present investigation was devoted to a comparison of the clinical and electrophysiological manifestations of experimental PS induced by damage to the DAergic neurons of the substantia nigra (SN) and by the direct hyperactivation of cholinergic neurons of the CN. In the first instance 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) and its metabolite, 1-methyl-4-phenylpyridinium (MPP+), which accord- ing to available data governs the toxic influence of MPTP on the DAergic neurons, was used to reproduce the PS [15,22,23].…”

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Features of the parkinsonian syndrome induced experimentally by a deficit of nigrostriatal dopamine and stimulation of cholinergic neurons of the caudate nuclei

Крыжановский

Atadzhanov

Воронина

et al. 1994

Neurosci Behav Physiol

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The Parkinsonian syndrome (PS) is reproduced experimentally by various methods which bring about a deficiency or ineffectiveness of the action of dopamine (DA) in the caudate nuclei (CN) [1,5,6,16]. Since DA exerts an inhibitory influence on the cholinergic neurons of the CN, the latter become disinhibited under the conditions of the ineffectiveness of the action of DA, and form a generator of pathologically enhanced excitation (GPEE) [5] which is the pathological basis of the PS [5,7]. By injecting into the CN substances which promote the hyperactivation of the cholinergic neurons and the formation of a GPEE, it is possible to induce an experimental form of the PS even without an insufficiency of DA and the DAergic apparatus. The phenomena of PS were reproduced by this method in animals of various species by the injection into the CN of oxytremorine, an agonist of the M-cholinoreceptors, and other cholinomimetics [18,21], as well as by the systemic administration of galantamine, a cholinesterase inhibitor [9].The present investigation was devoted to a comparison of the clinical and electrophysiological manifestations of experimental PS induced by damage to the DAergic neurons of the substantia nigra (SN) and by the direct hyperactivation of cholinergic neurons of the CN. In the first instance 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) and its metabolite, 1-methyl-4-phenylpyridinium (MPP+), which accord- ing to available data governs the toxic influence of MPTP on the DAergic neurons, was used to reproduce the PS [15,22,23]. The injection of MPP + directly into the SN induces marked degeneration of the DA neurons of the SN, a decrease in the content of striatal DA, and motoric disturbances which are characteristic for PS in rats and mice [23]. In the second instance the intracaudate injection of ACh and the systemic administration of oxytremorine were used for the direct activation of the cholinergic neurons of the CN. 485 METHODSThe experiments were carried out on 172 white mongrel male rats of various age groups (from 3 to 15 months), weighing 220-560 g, with chronically implanted electrodes.In experiment series I the rats were administered MPTP intraperitoneally, through cannulae implanted beforehand, in doses of 20-40 mg/kg over the course 10 days. MPP § iodide was injected once bilaterally into the SN in a dose of 10 lag in 2 lal of isotonic sodium chloride solution at a rate of 1 lal/min in series II. The animals in the control group were injected with sodium iodide in the same volume. In experiment series III, 5 lag of ACh in a volume of 1 lain [sic] along with 1 lag of proserine in a volume of 1 lal was injected into each of the rostral divisions of both CN at a rate of 1 lal/min. The animals in the control group were injected with isotonic sodium chloride in the same volume. Oxytremorine in a dose of I mg/kg intraperitoneally was administered once bilaterally in experiment series IV.

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